Process of treating phenols



Patented June20, 1944 PROCESS OF TREATING PHENOLS Lee Irvin Smith, Minne apolis, Minn., assirnor to Regents of the University of Minnesota, Minneapolis, Minn., a corporation 01' Minnesota No Drawing. Application July 14,1939, Serial No. 284,459

8 Claims.

This invention relates to methods for preparing substituted paraquinone and hydroquinone compounds, and more particularly, to methods for preparing the polyalkyl substituted derivatives of such compounds, such as polymethyiquinones and hydroquinones.

Paraquinone compounds of the aforementioned types, particularly the polyalliyl para hydroquinones, are of especial usefulness in the synthesis of products which exhibit the vitamin E eifects of the natural tocopherols, but they have heretofore been obtainable only by laborious and relatively inemcient synthesis from rare and expensive materials such pseudocumidine-5.

According to the present invention, it is possible to prepare the aforementioned paraquinone and hydroquinone materials with great facility from readily available and inexpensive materials such as phenolic compounds, and. it is accordingly an object of the present invention to provide methods for such preparation.

Specifically, it is an object of the invention to provide methods of preparing polyalkyl substituted paraquinones and hydroquinones from substituted phenol compounds in which the para position is vacant and in which there are at least one substituent group as an allyl group or a plurality of substituent groups such as alkyl groups. In the preferred method of carryi'ng out the present invention, a, selected substituted phenolic compound is first reacted with an aromatic diazonium salt to form an azo dye compound which is then reduced by appropriate treatment to the. corresponding amino phenol. The latter is then immediately reacted, upon by an oxidizing agent without separation from the incidentally regenerated aromatic amines and the quinone product produced and separated. The latter is then converted by reduction to the corresponding hydroquinone.

Sulfanilic acid is preferred for the initial reaction with the phenolic starting ingredient, although other aromatic diazonium compounds such as diazotized aniline may be used in specific procedures. For the reduction step stannous chloride is preferred, this reaction being carried out in the presence of an acid such as hydrochloric acid, and the reaction is carried on until the phenolic-aromatic azo-compiex is reduced through the hydrazo stage until the amino phenol is liberated. The aromatic amino compound is regenerated at this stage, but according to the preferred procedure, is not removed, the entire reaction mass being at once treated with a large excess of oxidizing agent, preferably ferric chloride, sufiicient to oxidize both the stannous chloride and the amino phenol. The desired quinone thus produced in situ is removed by immediate steam distillation. The thus liberated quinone may be converted quantitatively to the corresponding hydroquinone by reaction with zinc and acetic acid or by catalytic reduction.

The procedure of the present invention is shown in greater detail by the following examples, which are however, merely illustrative, and therefore must not be considered as limitations upon the invention. I

Example I A diazonium solution was first prepared by dis solving 105 grams of sulfanilic acid and 26.5 grams of sodium carbonate in 500 cc. of water.

Solution of the ingredients was accomplished by The diazonium solution thus prepared was then slowly poured into a well stirred solution of 63 grams (.5 mol) pseudocumenol 6 sometimes called 2,3,5-trimethy1 phenol, and 7.5 grams of sodium hydroxide in 300 cc. of water. Pseudocumenol-6 has the formula inc 4 3 2 on,

When the substance is named as a derivative of the hydrocarbon, pseudocumene, the numbering starts at the position ortho to the hydroxyl group; however, when the substance is named as a derivative of phenol, the numbering starts with the position at which the hydroxyl group is substituted, and -in that case, the formula is written and numbered as follows:

p modem and is known as 2,3,5-trimethyl phenol. The excess of alkali is important at this stage of the reaction. The mass was then permitted to stand for at least two hours and preferably longer, ai-

' methyl phenol used. In

lowing the ice (introduced by way of the diazonium solution) to melt and the temperature to rise to room temperature.

At this stage, the mass is a deep red color which denotes the existence of the azo dye compound.

The red dye reaction mass was made strongly acid by the addition of 200-250 cc. of (1 normal) hydrochloric acid and 164 grams of stannous chloride in 200 cc. of hydrochloric acid was then added. The mass was then heated almost to boiling until the solution cleared and the color became light orange brown.

Then, without separation of any ents, the mass was transferred to a steam distillation fiask and a large excess 800 grams) of ferric chloride was added. The steam distillation was begun immediately, so as to prevent the formation of the undesired chloroquinone compounds.

The quinone and steam were distilled over and the quinone compound (an oily liquid) was separated from the mixed condensate by extraction with ethyl ether. The extraction was continued until the aqueous layer of. the mixed condensate became colorless, as this quinone is fairly soluble in a large volume of water. The combined ether extractions were dried over sodium sulfate and the ether solvent removed by distilling it through a short packed column. The trimethyl quinone residue of 72 grams (95% yield) was solidified in an ice bath, and then melted at 26 C., and is suitable for most purposes. Where high purity is desired, the trimethyl quinone is distilled in vacuum, the boiling point being 98 C. under mm. of mercury pressure, and 108 C. under 18 mm. of mercury pressure.

Example II When a stoichiometric equivalent quantity of 3,5-dimethyl phenol is substituted for the pseudo cumenol-6 of the preceding example, the remainin reactants and reagents being used in proportional quantities, a metaxyloquinone, having a melting point of 7375 C. results, the yield. being 74.5% based upon the amount of 3,5dimethyl phenol used. The procedural details are as given for Example I.

' Example III When a stoichiometric equivalent quantity of 2,5-dimethyl phenol is used in place of the pseudocumenol-B of Example I, the remaining reactants and reagents being used in proportional quantities, paraxylo-quinone, having a melting point of 123.5-125" C. results, the yield being 50% based upon the amount of 2,5-dithis instance also, the procedural details are as given in Example I.

Example IV When a stoichiometric equivalent quantity of.

2,3,5,6-tetramethyl phenol (durenol) is used in place of the pseudocumenol-6 in Example I, the remaining reactants and reagents being used in proportional quantities, duroquinone having a melting point of Ill-112 C.-results, the yield being 60% based upon the amount of durenol used.

Example V of the ingreditwo hours. To the solution there was then added 4.53' grams of sodium hydrosulphite and the entire mixture was heated, with stirring until it reached 90 -C. whereupon it became colorless. Upon cooling a light yellow, needle crystalline product separated and was recovered by filtration, 1.7 grams of the crystalline product being obtained. To the separated crystalline product thus obtained, there was added an oxidizing solution consisting of 5.5 grams of ferric chloride hexahydrate in 5 cc. of water and 2 cc. of concentrated hydrochloric acid. Steam was then passed through the mixture, whereupon the quinone compound, which was a liquid, was ,driven ofi and was recovered from the steam distillate by extraction with ethyl ether, 1.43 grams of 2,3,5-trimethyl-6-allyl quinone being obtained.

Example VI ture of the quinone, zinc, acetic acid and water was heated under reflux for 15 minutes and the hydroquinone compound recovered by pouring the refluxed mixture into ice and water, the hydroquinone compound separating in the form of 'white needle-like crystals. The yield of trimethyl allyl hydroquinone thus formed was 1.16 grams.

Example VII In the procedure of Example I, diazotized aniline may be substituted for diazotized sulfanilic acid when suitable variations are provided in the procedure. Thus diazotized aniline was prepared by diazotizing 112 grams of aniline in 2400 cc. of sulphuric acid solution. The thus formed diazotized aniline was then reacted in alkaline solution with 126 grams pseudocumenol 6 .(sometimes known as 2,3,5-trimethyl phenol) and the red dye compound thus formed was filtered off and dried, 218 grams being recovered (98% yield).

Twenty grains of the thus separated red dye compound was then reacted upon by 50 grams stannous chloride and subsequently treated with ferric chloride and hydrochloric acid as described in Example I yielded 25 grams of 2,3,5-

ftrimethyl quinone, which was recovered by steam distillation followed by extraction with ethyl ether. The yield was 20.8% based upon the amount of pseudocumenol-6 used.

Example VIII Ten grams of the dried red dye compound of Example VII was reduced catalytlcally by suspending the dye compound in ethyl alcohol along grams or 2,3,5-trimethyl quinone (43%) having a boiling point of 98-103 C. under 11 mm. of mercury pressure.

Example IX In a procedure similar to that of Example VIII, 20 grams of the dry red dye compound of Example VII was suspended in 150 cc. of water and treated with hydrogen at 2000# pressure in the presence of Fancy nickel at 120 C. for 2 hours. The reaction mixture yielded 5 grams (41%) of 2,3,5-trimethyl quinone when thereafter treated as in Example VIII.

In the procedures of Examples VIII and IX, the catalytic reduction with hydrogen started at room temperatures when the high pressures (2000#) were used, but there was no reaction at low pressures (40#) even though the procedure was continued over long periods (15 hours).

One of the foremost advantages of certain of the procedures of the present invention is in the use of stannous chloride for reduction of the azo dye compounds, since separation of the reduced amino phenolic compounds is thereby rendered unnecessary, the entire reaction mass being treated wtih acidified ferric chloride all as set forth in Examples I through IV. High yields ranging from 50% in Example III to 95% in Example I are thereby made possible. The continuous procedure of Examples I through IV is not feasible where sodium hydrosulfite is used (Example V), or where the aromatic diazonium compound is derived from aniline, (Examples VII et seq.). In these, the azo dye compound is separated before reduction. From Examples I thru V it is apparent that the products resultant from the coupling of diazotized sulfanilic acid and the selected phenol may be reduced either by stannous chloride or sodium hydrosulflte, but hydrogen with a catalyst is unsuitable because of the well known poisoning effect of sulfur compounds on hydrogenation catalysts. Examples VII thru IX show that where diazotized aniline is utilized as one of the starting ingredients the reduction step may be accomplished by stannous chloride or hydrogen in the presence 01 a catalyst, sodium hydrogen being unsuitable.

The quinone compounds produced in accordance with the foregoing procedures may be reduced by many methods other than that set forth in Example VI. Thus they may be reduced catalytically by the use of hydrogen under pressure in presence of a catalyst such as Raney nickel, platinum oxide, palladium, or copper chromite, or they may be reduced by sulphur dioxide in the presence of water or by the use of various organic reducing agents.

Many obvious variations may be made in the foregoing procedures without departing from the spirit of the invention herein disclosed and claimed as follows.

I claim:

1. The process of preparing quinones which comprises reacting a substituted phenol of the benzene series in which the para position is vacant and which is a member of the group consisting of monoallyl substituted phenols, polyalkyl substituted phenols, and monoallylpclya kyl substituted phenols with an aromatic diazonium compound, treating the resultant admixture with 70 the presence of an acid.

stannous chloride in the presence of hydrochloric acid, then treating the reaction mass with an excess of ferric chloride in the presence of an acidulating substance and separating the thus formed quinone by steam distillation.

2. The process of preparing quinones which comprises reacting a substituted phenol or the benzene series in which the para position is vacant and which is a member of the group consisting of monoallyl substituted phenols, polyalkyl substituted phenols, and monoallylpolyalkyl substituted phenols with diazotized sulfanilic acid, then heating the mixture with stannous chloride in the presence of an acid, then treating the thus formed amino phenolic compound with an excess of ferric chloride in an acid medium. and simultaneously steam-distilling the reaction mass to remove the quinone.

3. The process of preparing quinones which comprises reacting a substituted phenol of the benzene series imwhich the para position is vacant and which is a member of the group consisting of monoallyl substituted phenols. polyalkyl substituted phenols, and monoallylpolyalkyl substituted phenols with diazotized sulfanilic acid, then reacting the mixture by heating the stannous chloride and hydrochloric acid, then treating the entire reaction mass with an excess of ferric chloride in an acid medium and simultaneously steam-distilling.

4. The process of preparing substituted para quinones which comprises reacting a substituted phenol of the benzene series having the para position vacant and which is a member of the group consisting of monoallyl substituted phenols, polyalkyl substituted phenols, and monoallylpolyalkyl substituted phenols with diazotized sulfanilic acid, heating the mixture with stannous chloride in the presence of an acid, and then steam distilling the reaction mass in the presence of an excess of ferric chloride in an acid medium.

5. The process of making 2,3,5-trimethylq1ilnone which comprises reacting 2,3,5-trimethylphenol and diazotized sulfanilic acid, heating the mixture with stannous chloride in the presence of an acid, andthen steam-distilling the reaction mass under acidic conditions in the presence of an excess of ferric chloride.

6. The process of making dimethyl para quinones which comprises reacting a dimethyl phenol of the benzene series having the para position vacant with diazotized sulfanilic acid, heating the mixture with stannous chloride and acid, and then steam-distilling the reaction mass under acidic conditions in the presence of an excess of ferric chloride in an acid medium. 7. The process of making tetramethylquinone which comprises reacting tetramethyl phenol having the para position vacant with diazotized sulfanilic acid, heating the mixture with stannous chloride in the presence of an acid, and then steam distilling the reaction mass in the prmence of an excess of ferric chloride in an acid medlum.

8. The process of preparing 2,3,5-trimethyl para quinone which comprises reacting 2,3,5-trimethyl phenol with diazotized sulfanilic acid,

heating the mixture with stannous chloride in the presence of an acid, steam-distilling the time heated mass with an excess of ferric chloride in LEE mvm sMrrrL 

